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Year : 2019  |  Volume : 13  |  Issue : 25  |  Page : 1-9  

A comprehensive review on eugenol's antimicrobial properties and industry applications: A transformation from ethnomedicine to industry

1 Department of Pharmaceutical Chemistry, School of Pharmacy; School of Postgraduate Studies; Centre for Bioactive Molecules and Drug Delivery (BMDD), Institute for Research, Development and Innovation (IRDI), International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
2 Department of School of Postgraduate Studies, Institute for Research, Development and Innovation (IRDI), International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
3 Department of Medical Microbiology and Parasitology, Kaduna State University, Kaduna, Nigeria
4 Department of Chemistry, Central University of Karnataka, Gulbarga, Kanataka, India
5 Department of Pharmaceutical Chemistry, School of Pharmacy, Institute for Research, Development and Innovation (IRDI), International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
6 Faculty of Medicine, MAHSA University, Selangor, Malaysia
7 Institute of Science, University Teknologi MARA, Selangor, Malaysia
8 Department of Pharmaceutical Chemistry, School of Pharmacy; Centre for Bioactive Molecules and Drug Delivery (BMDD), Institute for Research, Development and Innovation (IRDI), International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia

Date of Web Publication3-Apr-2019

Correspondence Address:
Dr. Mallikarjuna Rao Pichika
Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/phrev.phrev_46_18

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Eugenol and eugenol-containing plants are used in ethno and modern medicine for various biological activities including antimicrobial activity. This review article provides an insightful transformation of eugenol from being an ethnomedicine to being a food protectant in the food industry. Scientific publications on the antimicrobial activity of eugenol and its respective advancements were collected from scientific databases such as Scopus, PubMed, and Google Scholar published between 1995 and June 2018. The eugenol has shown significant broad-spectrum antimicrobial activities against Gram-positive, Gram-negative, fungi, and virus. The eugenol has also shown synergistic effects with conventional antimicrobials. Formulations, such as micro- and nanoemulsions, nanocapsules, and nanoparticles, are prepared to improve the aqueous solubility and efficacy of eugenol. Eugenol is used as a food protectant in storing plants, grains, fruits, and livestock. This review covers eugenol's antimicrobial activities, formulations to improve aqueous solubility, and applications in the food industry. Extensive scientific investigations validated the ethnomedicinal uses of eugenol as an antimicrobial agent. Its activity on multidrug-resistant pathogens should further be explored to identify the molecular mechanisms and synergistic/antagonistic effects with conventional antimicrobials. There were no studies on investigating eugenol's potential in in vivo infectious animal models. This is the first review on eugenol that details the antimicrobial potential of eugenol and its possible applications as a protectant in the food industry.

Keywords: Antimicrobial, antiviral, essential oil, eugenol, food protectant, food industry

How to cite this article:
Mak KK, Kamal MB, Ayuba SB, Sakirolla R, Kang YB, Mohandas K, Balijepalli MK, Ahmad SH, Pichika MR. A comprehensive review on eugenol's antimicrobial properties and industry applications: A transformation from ethnomedicine to industry. Phcog Rev 2019;13:1-9

How to cite this URL:
Mak KK, Kamal MB, Ayuba SB, Sakirolla R, Kang YB, Mohandas K, Balijepalli MK, Ahmad SH, Pichika MR. A comprehensive review on eugenol's antimicrobial properties and industry applications: A transformation from ethnomedicine to industry. Phcog Rev [serial online] 2019 [cited 2019 Sep 19];13:1-9. Available from: http://www.phcogrev.com/text.asp?2019/13/25/1/255393

   Introduction Top

Despite the recognition of the ever-growing problem, global prevalence of microbial infections and associated health concerns continue to take a toll, resulting in increased cases of prolonged illness and death. This is worsened by increasing antimicrobial resistance that poses threats to the effective prevention and treatment of microbial infections. With this concern, various natural or synthetic compounds are actively explored for their efficacy in combating microbes. Eugenol, which is the major natural component found in clove oil, has been known for its versatility in pharmacological activities such as anti-inflammatory,[1],[2] anticancer,[3],[4],[5] analgesic,[6],[7] and anesthetic activities.[8],[9],[10] The chemical structure of eugenol is shown in [Figure 1].
Figure 1: Chemical structure of eugenol (C10H12O2). Eugenol's IUPAC name is 2-methoxy-4-(2-propenyl) phenol

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The eugenol is extracted from various plants such as cloves,[6],[11],[12],[13] lemon grass,[14],[15],[16] tulsi,[17],[18] and cinnamon[19],[20] via numerous methods of extraction including steam distillation, microwave-assisted extraction, supercritical carbon dioxide extraction, and ultrasound-based extraction.[21] This prominent compound offers a number of therapeutic benefits via inhibition of generative reactive oxygen and nitrogen species, scavenging of free radicals, and disruption of biofilms of microbes.[21],[22] The efficacy of eugenol and its mechanism of action against bacteria, fungi, and viruses are of interest. Due to the increasing incidence of microbial resistance to conventional antibiotics, the effects of eugenol that could work synergistically with the current antibiotics to improve their antimicrobial efficacy against different microbial strains were compiled and explicated. The applications of eugenol and its formulations in the food industry and antimicrobial activity of eugenol containing essential oils/plant extracts were also compiled as shown in [Figure 2].
Figure 2: The multifaceted applications of eugenol

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   Antibacterial Activity Top

One of the predominant causes of bacterial infections arises from biomaterial implant failures or bacterial adherence and biofilm formation on medical implants.[23] The prevalence of medical implants is increasing extensively in the past decades, and implant failure leads to relentless challenges in the medical field as its application.[24] Accordingly, a hydrophilic copolymeric system using eugenol was tested and it showed success in inhibiting bacterial growth.[25] Eugenol has been scientifically proven to be pharmacologically active against a number of bacteria, both Gram-negative and Gram-positive, as well as fastidious and facultative anaerobic oral bacteria.[26] The current data that could substantiate these claims are concisely summarized in [Table 1].
Table 1: Bacteria that are susceptible to eugenol in in vitro experimental models

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Eugenol is capable of significantly increasing the permeability profile of the membrane and has disruptive action on cytoplasmic membrane.[27] In addition, findings on the efficacy of eugenol suggest that inhibition of the production of virulence factors such as violacein, elastase, pyocyanin, and biofilm formation was successful.[28] Eugenol has also displayed high efficacy as an antistaphylococcal and antilisterial biofilm agent.[29]

In other industries – in broiler chicken for instance – eugenol-supplemented poultry feed reduces  Salmonella More Details enterica serovar Enteritidis colonization in chickens.[30] In the management of livestock waste on the other hand, eugenol has shown effectiveness in the inhibition of fermentation gas production, short-chain volatile fatty acids, and lactate and bacterial pollution in addition to its ability to stimulate lactate formation in cattle and swine waste.[31]

Resistant strains

Antibacterial effects of eugenol on multidrug-resistant bacteria also exhibited promising results. For instance, the Salmonella spp., Salmonella typhimurium SGI 1 (tet A), a Gram-negative bacterium that notably causes diseases of the intestines, is known to show resistance toward ampicillin, tetracycline, penicillin, bacitracin, erythromycin, and novobiocin (FIC <0.4) and nalidixic acid-resistant Salmonella enteritidis.[32] In contrast, the effects of eugenol on the aerotolerant Gram-positive Streptococcus pyogenes ermB to erythromycin (FIC <0.5) showed synergistic effects with ampicillin, tetracycline, penicillin, erythromycin, and novobiocin.[33]

Mechanisms investigated

To study the antibacterial studies of eugenol, a few discoveries regarding their mechanisms were made. The eradication of bloody diarrhea-causing agents such as Pseudomonas aeruginosa and enterohemorrhagic  Escherichia More Details coli was also possible as eugenol was found to successfully reduce the production of pyocyanin and PQS as well as inhibit the EHEC biofilm formation, respectively.[34] Eugenol was proven to possess the potential of a favorable target in the antibacterial area as it has the capabilities of downregulating YidC, a highly conserved bacterial protein which plays a vital role in membrane protein insertion.[35] In addition, eugenol showed competence in the inhibition and eradication of biofilms produced by methicillin-resistant and sensitive Staphylococcus aureus.[36] Another supporting study demonstrated membrane disruption in the bactericidal activity of E. coli, Listeria monocytogenes, and Lactobacillus sakei; this was achievable via the inhibition of their respective ATPase.[37] It is also believed that eugenol decreases the virulence factors that are produced by E. coli such as VT1 and VT2.[38] Another interesting finding involves the ability of eugenol to inhibit the FtsZ assembly that leads to the disruption of bacterial cell division.[39] It was also found that the effects of eugenol in downregulating the transcription of genes associated with Acinetobacter baumannii biofilm production contributed to the source of biofilm inhibition as well as disrupting the biofilm architecture.[40]

Synergistic effect

In addition to eugenol being used exclusively as a singular antibacterial agent, it has also successfully shown a synergistic effect with a few well-known antibacterial medications against various strains of bacteria as tabulated in [Table 2].
Table 2: The synergistic effect of eugenol with current medications in combating bacteria

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   Antifungal Activity Top

Like antibacterial agents, new and potent antifungal agents are also invariably and actively discovered. Despite the discovery of many new antifungal agents which have greatly improved the treatment of invasive mycoses, these newer antifungal agents still face challenges as they present toxicity associated with long-term use;[41] therefore, the discovery of new antifungal agents with better safety profiles is highly driven by the side effects of current conventional antifungal medication and fungal resistance.[42]

Eugenol has exhibited significantly favorable antifungal activity on various preformed biofilms, adherent cells, subsequent biofilm formation, and cell morphogenesis of Candida albicans[43],[44] without instigating hemolytic activity in human erythrocytes.[43] The battle to deal with fungal infections in its numerous guises has been on-going for the past few decades. The assortment of strains of fungus that are currently proven to be susceptible to eugenol is summarized in [Table 3].
Table 3: Fungus strains that are susceptible to eugenol

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Resistant strains

Remarkably, eugenol displayed tremendous fungicidal activity against isolates of pathogenic yeasts that have shown resistance toward azoles, and this was due to the inhibition of H+-ATPase activity.[45] Antigonorrheal activity was also shown in a number of multi-resistant strains of  Neisseria More Details gonorrhoeae.[46] Interestingly, eugenol was found to be more active against fluconazole-resistant Candida dubliniensis than synthetic antiseptic chlorhexidine gluconate, cetylpyridinium chloride, and triclosan.[47]

Mechanisms involved

It is believed that cell wall alteration contributes to the attainment in antifungal activity of eugenol against Saccharomyces cerevisiae.[48] The fungicidal causative effects of eugenol in C. albicans are mainly due to the disruption of membrane integrity[44] as well as significantly weakening the defense system through free radical cascade-mediated LPO, which subsequently leads to membrane lesions.[49] Interestingly, the interference with amino acid permeases contributes to the inhibitory effect of eugenol. A study has shown inhibitory effects of eugenol on two permeases (Tat1p and Gap1p) that are responsible for the transport of amino acids through the yeast cytoplasmic membrane.[50] In addition, the synergistic antifungal effect of eugenol with cinnamaldehyde is a result of the interference of fungal cell wall synthesis as well as cell wall destruction in addition to a radical scavenging effect.[51]

Synergistic effect

The synergistic effects of eugenol with currently available antifungal drugs and other compounds are listed in [Table 4].
Table 4: The synergistic effect of eugenol with current medication in combating fungi

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   Antiviral Activity Top

As a potent natural product, eugenol is heavily investigated to understand its biological activity and therapeutic potential as an antimicrobial agent. There is also the synergistic effect between eugenol and acyclovir in the inhibition of herpes virus in vitro; on its own, topical application of eugenol was found to delay the growth of herpes virus-induced keratitis in mouse models.[38] Eugenol displayed antiprotozoal activity against Leishmania, which is an assembly of diseases responsible for a wide spectrum of clinical manifestations,[52] ovicidal activity against Haemonchus contortus, a parasite that resides in the gastrointestinal tract[53] and virucidal activity against HSV-1 and HSV-2 viruses.[54],[55]

   Essential Oils Top

Eugenol essential oil can be extracted from plant sources, such as cloves, cinnamon, tulsi, and pepper[56],[57],[58] as well as the leaves of Lippia multiflora, Mentha piperita, and Ocimum basilicum from Burkina Faso.[59] Eugenol is commonly the main constituent in these plants, and this essential oil has prospects as a nutraceutical. Among many beneficial effects induced by eugenol such as anti-inflammation, anti-hyperglycemia and anticancer, it is also a highly potent antimicrobial agent.[21],[60]


Eugenol essential oil showed potent anthelmintic activity in a Caenorhabditis elegans model.[61] A few essential oils extracted from flowering plants showed antibacterial activity. For instance, eugenol essential oil is extracted from Syringa oblata flower buds against Ralstonia solanacearum[62] and Syzygium aromaticum flower buds against Leishmania donovani.[63]

The essential oil of eugenol and its interaction with ten antibiotics of hydrophobic and hydrophilic characteristics were studied against Gram-negative bacteria.[64]


As previously discussed, eugenol essential oil conferred antifungal activity against Fusarium oxysporum f. sp. Lycopersici 1322, which suggests that eugenol can be used in preventive and therapeutic applications.[65] Eugenol extracted from the essential oil of Piper divaricatum showed activity against cladosporioides and Cladosporium sphaerospermum[66] while essential oil from Nephrolepis exaltata and Nephrolepis cordifolia showed antibacterial and antifungal activities.[67] The eugenol-containing essential oil extracted from Cinnamomum verum, S. aromaticum, Cymbopogon citratus and Cymbopogon martini were found to transform the hyphal ultrasound and virulence factors of Aspergillus fumigatus and Trichophyton rubrum.[68] Eugenol from Ocimum sanctum showed activity against Aspergillus flavus NKDHV8 that causes biodeterioration of food stuff.[69] It was also reported that volatile oil of Cinnamomum zeylanicum Blume' s leaves and barks showed fungal inhibitory activity against A. flavus, Aspergillus ochraceus, Aspergillus niger, Aspergillus terreus, Penicillium citrinum, and Penicillium viridicatum. The antifungal activity of eugenol-containing essential oils is summarized in [Table 5].
Table 5: Source of eugenol essential oil extracts and their respective susceptible strains

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   Formulations Top

Beyond its role as a simple antimicrobial agent, eugenol was investigated in numerous formulations. Eugenol/cyclodextrin inclusion complexes encapsulated in electrospun polyvinyl alcohol nanofibers were shown to have enhanced thermal stability and subsequently result in the slow release of eugenol.[70] Eugenol-containing microemulsion can be prepared by simply solubilizing the eugenol (0.75–1.5 wt.%) essential oil in surfactant micelles (Surfynol 465; 5–10 wt. %).[71] In addition, findings from another study reported that eugenol-incorporated micelles had higher efficacy than that of pure application of eugenol.[72]

A variety of formulated products that incorporated eugenol were found to be potent. The consecutive application of eugenol and lauric arginate was shown to inhibit the growth of Staphylococcus carnosus, Listeria innocua, L. monocytogenes, E. coli (K12 and O157:H7), Pseudomonas fluorescens, and S. enteritidis.[73],[74] Synergistic antimicrobial activity was exhibited in the multi-agent formulation comprising eugenol/beta-pinene/salicylic acid and eugenol/beta-pinene/2-phenoxyethanol/potassium sorbate where the mechanism is facilitated via cellular permeabilization in addition to inhibition of efflux pump activity.[75] Another formulation that yielded higher antimicrobial activity than that of eugenol itself is the inclusion complex between water-soluble β-cyclodextrin-grafted chitosan derivatives (βCD-g-CS) and eugenol to produce a mucoadhesive drug carrier. This formulation has potent antimicrobial activity against C. albicans, S. oralis, and S. mutans[76] and antifungal activity against Peronophythora litchi.[77]

Aqueous solubility

Eugenol is sometimes encapsulated as it can improve the water solubility profile; such preparation showed growth inhibition of E. coli O157:H7 (H1730, F4546, 932, and E0019) and L. monocytogenes (Scott A, 101, 108, and 310).[78] Another way of improving the water solubility profile is by formulating eugenol as nanoparticles in water-based microemulsion systems.[60]


Microemulsions of eugenol inhibited the growth of foodborne pathogens such as L. monocytogenes, E. coli (O157:H7 and C 600), and L. innocua completely.[112],[113] Formulated carbopol hydrogels incorporated with eugenol-loaded solid lipid nanoparticles (EG-SLN) were beneficial for the epidermal treatment in the attempt to treat fungal infection in the skin.[81] Various nanoemulsions with incorporated eugenol were prepared and tested against different pathogens. For example, sesame oil-blended eugenol-loaded nanoemulsion displayed antibacterial activity against S. aureus,[82] eugenol-chitosan particles exhibited significant antibacterial activity against E. coli and S. aureus,[83] and eugenol-beta-cyclodextrin nanoparticles showed antivirulence activity against E. coli and S. aureus.[84] Dispersion of eugenol in nanocapsules formulated with conjugates of whey protein isolate and maltodextrin also showed potency against E. coli O157:H7 strains ATCC 43889 and 43894 and L. monocytogenes strains Scott A and 101.[85] Encapsulation of eugenol in poly (DL-lactide-co-glycolide) (PGLA) nanoparticles enhanced its antimicrobial delivery against the growth of Salmonella spp and Listeria spp.[86] Solid lipid nanoparticles (SLN) loaded with eugenol showed in vivo antifungal activity in immunosuppressed rats of oral candidiasis.[87] A gum Arabic and lecithin-eugenol incorporated nanoemulsion prepared as a food-grade natural emulsifier successfully displayed antimicrobial activity against L. monocytogenes and S. enteritidis.[88]

The significant leishmanicidal activity of eugenol against promastigotes and intracellular amastigotes of L. donovani carried out in vitro and in vivo was shown when it was formulated in an oil-in-water emulsion.[89] In addition, eugenol emulsions showed antibacterial activity against Xanthomonas campestris pv. Phaseoli var. fuscans.[90] The eugenol-incorporated formulations reported in the literature and their respective antimicrobial activities are summarized in [Table 6].
Table 6: Summary of current eugenol-incorporated formulations in the enhancement of antimicrobial activity

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   Applications in the Food Industry Top

Productive applications in science stem from the ability to connect unanticipated observations to develop new areas of explorations – the usage of eugenol in the food industry for instance. From the identification of eugenol as a potent antimicrobial agent, it has been gradually introduced to the food industry [Table 7]. Some of the most prevalent foodborne pathogenic bacteria affected by the antibacterial activity of eugenol include S. aureus, E. coli, S. enterica serovar Typhimurium, and L. monocytogenes[91],[92],[93] and fungi comprising Cladosporium spp. (MIC: 100 mug/mL), Aspergillus spp. (MIC: 100 mug/mL), Cladosporium spp. (MIC: 350 mug/mL), and Aspergillus spp. and Cladosporium spp. as shown in [Table 2].[98]
Table 7: List of pathogens that are susceptible to the antimicrobial activity of eugenol

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Plants and grains

The potency of eugenol as a prospective biocontrol agent in grains was suggested as it contributes to the inhibition of ochratoxin A production caused by A. ochraceus – a frequent contaminant found in the storage of grains.[94] Another possibility is to diminish the population of Salmonella in soil to reduce probable contamination of fresh organic produce.[95]


The broad spectrum of eugenol's protective effects can be observed in various foodborne pathogens. Eugenol worked against the common nalidixic acid-resistant S. enteritidis found in contaminated eggs[32],[96],[97] and it was found to inhibit the growth and colonization in the chicken reproductive tract.[98] In a more general application, eugenol was capable of enhancing food safety and stability without instigating any bacterial adaptation of S. enterica serovar Typhimurium.[99] Treatment and prevention of bacterial diseases in fish is also possible as eugenol is active against a fish pathogen called A. hydrophila without posing toxicity effects to the fish.[100]


In the fruit sector, eugenol has been commonly used as fungicides. Eugenol was found to inhibit the growth of fungi that causes decay of strawberries.[101] Eugenol oil inhibited the growth in both in vitro and in vivo tests of numerous apple fungus, namely P. vagabunda, P. expansum, B. cinerea, and Monilinia fructigena.[102] A few fungi such as Sclerotinia sclerotiorum (Lib.), R. stolonifera (Ehrenb. ex Fr.) Vuill, and Mucor spp. (Fisher) cause deterioration and decay in peaches especially during marketing, shipping, and storage; eugenol works synergistically with linalool as a potent fungicide.[103]

In a study looking at the type of microflora that are responsible in fruit juice spoilage, eugenol was also biologically active against foodborne bacteria such as L. plantarum, L. brevis, and B. coagulans and foodborne yeasts such as Saccharomyces bayanus, Pichia membranifaciens, and Rhodotorula bacarum.[104]

Shelf life

Eugenol is incorporated into polyhydroxybutyrate-based antimicrobial films as an approach to enhance the shelf life of food.[105] As a preservative, positive results were also observed against S. cerevisiae and Zygosaccharomyces bailii.[106]

Certain results suggest a mechanism that involves the inhibition of tumor necrosis factor-inducing and hemolytic activities of S. aureus supernatants by reducing the production of staphylococcus enterotoxin A and B and toxic shock syndrome toxin 1 as well as the expression of alpha-hemolysin.[107]


The authors would like to thank the International Medical University for the facilities and the Ministry of Higher Education for their financial support.[139]

Financial support and sponsorship

The study was funded by the ERGS grant from the Ministry of Higher Education of Malaysia (ERGS/1/2012/STG01/IMU/02/1).

Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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